Biomedical subjects
S Clements
Publications and source records attributed to S Clements.
Novel multigene families encoding highly repetitive peptide sequences. Sequence analyses of rat and mouse proline-rich protein cDNAs.
Multigene families encode the proline-rich proteins that are so prominent in human saliva and are dramatically induced in mouse and rat salivary glands by isoproterenol treatment and by feeding tannins. A cDNA encoding an acidic proline-rich protein of rat has been sequenced (Ziemer, M. A., Swain, W. F., Rutter, W. J., Clements, S., Ann, D. K., and Carlson D. M. (1984) J. Biol. Chem. 259, 10475-10480). This study presents the nucleotide sequences of five additional proline-rich protein cDNAs complementary to both mouse and rat parotid and submandibular gland mRNAs. Amino acid compositions deduced from the nucleotide sequences are typical for proline-rich proteins: 25-45% proline, 18-22% glycine, and 18-22% glutamine and generally an absence of sulfur-containing amino acids except for the initiator methionine. These proline-rich proteins display unusual repeating peptide sequences of 14-19 amino acids. The derived amino acid sequence of the cDNA insert of plasmid pMP1 from mouse has a 19-amino acid sequence which is repeated four times. The inserts of plasmids pUMP40 and pUMP4 also from mouse encode for 12 and 11 repeats of a 14-amino acid peptide, respectively. These repetitive sequences, and others from rat and mouse cDNAs and from human genomic clones, all show very high homologies and likely evolved from duplication of internal portions of an ancestral gene. Gene conversion could account for the high degree of conservation of nucleotide sequences of the repeat regions. Protein derived from the nucleotide sequences are all characterized by four general regions: a putative signal peptide, a transition region, the repetitive region, and a carboxyl-terminal region. The 5'-flanking sequences and sequences encoding the putative signal peptides are highly conserved (greater than 94%) in all six cDNAs. This sequence conservation may be important in the regulation of the biosynthesis of these unusual proteins.
Induction of proline-rich glycoprotein synthesis in mouse salivary glands by isoproterenol and by tannins.
Glycoproteins which contain about 45 mol% proline were dramatically induced in mouse parotid and submandibular glands by isoproterenol treatment, but these unusual proteins were not detected in control animals. These acid-soluble substances were obtained by extracting tissues with 10% trichloroacetic acid, as reported previously for isolating proline-rich proteins from rat submandibular glands (Mehansho, H., and Carlson, D.M. (1983) J. Biol. Chem. 258, 6616-6620). Three major proline-rich glycoproteins were induced in parotid glands with apparent molecular weights of 66,000 (GP-66p), 45,000 (GP-45p), and 27,000 (GP-27p), whereas only one such protein was expressed by the submandibular glands (66,000 (GP-66sm]. Both GP-66p and GP-66sm contained about 19% carbohydrate with the following molar ratios, respectively; GalNAc, 1.0, 1.0; Gal, 1.6, 2.3; GlcNAc, 0.8, 1.1; sialic acid, 0.9, 1.9. The peptide chains of GP-66p and GP-66sm appear to be identical by amino acid compositions, glycopeptide analysis, and preliminary amino acid sequencing data. Northern blot analysis of RNAs from parotid glands of normal and isoproterenol-treated rats, probed with a 32P-labeled proline-rich protein cDNA, confirmed that control animals were devoid of mRNAs encoding these proteins and that isoproterenol treatment dramatically induced expression of these genes. Feeding sorghum high in tannins caused changes in the parotid glands similar to those observed upon isoproterenol treatment, as noted earlier with rats (Mehansho, H., Hagerman, A., Clements, S., Butler, L., Rogler, J., and Carlson, D.M. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3948-3952). These glycoproteins have high affinities for tannins as demonstrated by competitive binding curves.
Salivary proline-rich protein genes on chromosome 8 of mouse.
Endonuclease restriction (Hind III) fragments of DNA from Chinese hamster X mouse somatic cell hybrids hybridized with proline-rich protein complementary DNA clones only when the DNA was isolated from cells containing mouse chromosome 8, or a fragment of chromosome 8. The evidence suggests that proline-rich protein genes are located at the proximal portion of chromosome 8 toward the centromere.
Nucleotide sequence analysis of a proline-rich protein cDNA and peptide homologies of rat and human proline-rich proteins.
Plasmids containing cDNAs for proline-rich proteins have been isolated from a cDNA library prepared from parotid glands of isoproterenol-treated rats. The nucleotide sequence of one of these cDNAs (pRP33) has been determined, and it encodes an acidic proline-rich protein. The N-terminal 13 amino acids are highly hydrophobic and may be part of a signal peptide. The next 66 amino acids constitute an acidic domain which is interrupted by a short (8 residue) basic region. The sequence beginning at proline 80 contains six tandemly repeated regions of 18 to 19 amino acids in length with the prototype sequence PPPQGGPQXPPQPGXPQG. Two pairs of these repeats (amino acid residues 116 to 152 and 153 to 189) are 93% homologous in nucleotide sequence. The high homology in both nucleotide and amino acid sequences in the repeat region suggests that this protein may have evolved by duplication of internal portions of a progenitor gene.
Modulation of proline-rich protein biosynthesis in rat parotid glands by sorghums with high tannin levels.
Feeding of sorghum with a high level of tannin (high-tannin sorghum) to rats caused changes in gene expression in parotid glands similar to isoproterenol treatment. Within 3 days the parotid glands were enlarged about 3-fold and a series of proline-rich proteins were increased about 12-fold. Unlike isoproterenol treatment, no changes were observed in the submandibular glands, and a Mr 220,000 glycoprotein in parotid glands was not induced. Amino acid analyses, electrophoretic patterns, and cell-free translations of mRNAs all confirmed that the proline-rich proteins induced by feeding high-tannin sorghum were identical to those induced by isoproterenol treatment. Binding curves for proline-rich proteins to tannins showed affinities 10-fold greater than bovine serum albumin and tannins.
Aortic stenosis: echocardiographic cusp separation and surgical description of aortic valve in 22 patients.
Diminished echocardiographic aortic cusp separation is used as one indicator of the severity of aortic stenosis. To test the validity of this index, 22 patients--12 (55 percent) with isolated aortic valve disease and 10 (45 percent) with aortic stenosis associated with mitral or coronary artery disease--underwent M mode echocardiographic examination before aortic valve replacement. Tracings of diagnostic quality were obtained without difficulty from all 22 patients. Cardiac catheterization was performed in 21 patients. Echocardiographic cusp separation was measured from the apparent mid-systolic orifice and from the outer periphery of the anterior cusp to the outer periphery of the posterior cusp (maximal peripheral cusp separation). Mid-systolic cusp separation varied in nearly every patient, depending on the angle of leaflet presentation to the ultrasonic beam. Maximal peripheral cusp separation measured 16 mm in 18 of 22 patients (82 percent); it indicated neither the severity of the aortic stenosis as documented with cardiac catheterization nor the mobility of the cusps seen at operation. The surgical and echocardiographic descriptions of leaflet and aortic root calcification were similar. In situ examination of aortic cusp separation indicated that diseased aortic valves are not comparable with normal valves or valves with uncomplicated congenital obstruction. The aortic leaflets were curled, fused, calcified and deformed from their natural state of coaptation. Abnormal thickening and limited or eccentric mobility of the aortic leaflets were useful indicators of the cause of valve disease, but cusp deformity secondary to aortic stenosis invalidated mid-systolic cusp separation and maximal peripheral cusp separation as indicators of the severity of aortic stenosis.
Focus on disability. Aids to disabled living.
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Refractory chronic fatigue syndrome in adolescence.
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